The purpose of the proposed research is to develop a method of using cultured thymic epithelium in various types of immunodeficiency. In so doing, it is our intent to come to a greater understanding of mechanisms of thymic differentiation as well as define the clinical conditions which might benefit from this therapy. The ability to improve the immunity of various patients will also provide greater insight into the nature of thymic influence in mechanisms of immunity. In vitro and in vivo studies will be performed. In vitro, cultured thymic epithelium will be used with various lymphoid cell preparations and the degree of T and B cell differentiation measured by using cell surface markers and various in vitro responses characteristic of differentiated T and B cells. The morphology of interaction will be studied. In vivo, restitution of of nude mice, neonatally thymectomized rabbits and patients with various immunodeficiency disorders will be attempted. Analysis of the degree of restitution will be accomplished by standard in vitro tests of component T and B cell function, morphological studies of lymphoid tissue and clinical improvement.